ИСТИНА

Environmental factors in the neonatal period influence the development of the adult phenotype through epigenetic modifications, including histone acetylation (Weaver et al., 2004, 2006). However, the long-term effects of pharmacological modulation of these molecular mechanisms have not been investigated. The effects of histone deacetylase inhibition during the first week of life by sodium valproate on the adult mice behavioral phenotype were investigated. The injections of sodium valproate (50 mg/kg s.c.) were accompanied by 45-min maternal deprivation on postnatal days 3-6. The other group was exposed to maternal deprivation only. Intact group received no manipulations. On postnatal day 7, the level of histone acetylation in the brain was determined using Western blotting analysis. On day 8, pups were trained in an olfactory associative learning task and were tested 24 hours later. Adult males underwent a battery of behavioral tests: open field, elevated plus-maze, contextual fear conditioning, and spontaneous alternation in a T-maze. In the early postnatal period, valproate injections ameliorated the effects of maternal deprivation at the molecular and behavioral levels. In adult males, deprivation negatively affected contextual fear memory formation and valproate administration had no effect on long-term memory. Emotional behavior was not affected by maternal deprivation, while administration of sodium valproate altered emotionality of adult males. Supported by RFBR Grant 14-04-01768